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Since the inception of next-generation mRNA sequencing (RNA-Seq) technology, various attempts have been made to utilize RNA-Seq data in assembling full-length mRNA isoforms de novo and estimating abundance of isoforms. However, for genes with more than a few exons, the problem tends to be challenging and often involves identifiability issues in statistical modeling. We have developed a statistical method called "sparse linear modeling of RNA-Seq data for isoform discovery and abundance estimation" (SLIDE) that takes exon boundaries and RNA-Seq data as input to discern the set of mRNA isoforms that are most likely to present in an RNA-Seq sample. SLIDE is based on a linear model with a design matrix that models the sampling probability of RNA-Seq reads from different mRNA isoforms. To tackle the model unidentifiability issue, SLIDE uses a modified Lasso procedure for parameter estimation. Compared with deterministic isoform assembly algorithms (e.g., Cufflinks), SLIDE considers the stochastic aspects of RNA-Seq reads in exons from different isoforms and thus has increased power in detecting more novel isoforms. Another advantage of SLIDE is its flexibility of incorporating other transcriptomic data such as RACE, CAGE, and EST into its model to further increase isoform discovery accuracy. SLIDE can also work downstream of other RNA-Seq assembly algorithms to integrate newly discovered genes and exons. Besides isoform discovery, SLIDE sequentially uses the same linear model to estimate the abundance of discovered isoforms. Simulation and real data studies show that SLIDE performs as well as or better than major competitors in both isoform discovery and abundance estimation. [ABSTRACT FROM AUTHOR]

High-resolution gridded datasets of meteorological variables are needed in order to resolve fine-scale hydrological gradients in complex mountainous terrain. Across the United States, the highest available spatial resolution of gridded datasets of daily meteorological records is approximately 800 m. This work presents gridded datasets of daily precipitation and mean temperature for the East–Taylor subbasin (in the western United States) covering a 12-year period (2008–2019) at a high spatial resolution (400 m). The datasets are generated using a downscaling framework that uses data-driven models to learn relationships between climate variables and topography. We observe that downscaled datasets of precipitation and mean temperature exhibit smoother spatial gradients (while preserving the spatial variability) when compared to their coarser counterparts. Additionally, we also observe that when downscaled datasets are upscaled to the original resolution (800 m), the mean residual error is almost zero, ensuring no bias when compared with the original data. Furthermore, the downscaled datasets are observed to be linearly related to elevation, which is consistent with the methodology underlying the original 800 m product. Finally, we validate the spatial patterns exhibited by downscaled datasets via an example use case that models lidar-derived estimates of snowpack. The presented dataset constitutes a valuable resource to resolve fine-scale hydrological gradients in the mountainous terrain of the East–Taylor subbasin, which is an important study area in the context of water security for the southwestern United States and Mexico. The dataset is publicly available at 10.15485/1822259 (Mital et al., 2021). [ABSTRACT FROM AUTHOR]

Longitudinal studies involving weekly measurement of urinary oestrogen and pregnanediol excretion were performed in 55 post-partum women to identify the patterns of returning fertility. The women kept diaries of breast-feeding episodes, mucus symptoms and times of bleeding; some recorded basal body temperature and acts of intercourse. The study represented a total time of 36 years (7·8 months per woman). The majority of the women were breast-feeding throughout the study. During lactation amenorrhoea, there was complete ovarian quiescence in two-thirds of the subjects and minimal cyclic activity in the others. The first bleeds were associated with anovulatory ovarian activity in 40% of the women, with normal ovulation in 19%, with ovulation but short luteal phases in 25% and with ovulation but deficient luteal phases in 16%. The incidence of normal ovulatory cycles increased with time after delivery and with the number of cycles after delivery and eventually reached 85% even though many women were still breast-feeding at the time. Twenty-two pregnancies occurred, fourteen being unplanned: eight women were fully breast-feeding at the time of conception. Mucus symptoms correlated with the hormone values in approximately 60% of cycles. However, some women had symptoms which were difficult to interpret during their early cycles or potential fertility was not indicated by raised mucus scores or the presence of the peak mucus symptom. These problems together with the resulting confusion appeared to be the major causes for the unplanned pregnancies. Methods for coping with these problems are discussed. [ABSTRACT FROM AUTHOR]

High resolution gridded datasets of meteorological variables are needed in order to resolve fine-scale hydrological gradients in complex mountainous terrain. Across the United States, the highest available spatial resolution of gridded datasets of daily meteorological records is approximately 800 m. This work presents gridded datasets of daily precipitation and mean temperature for the East-Taylor subbasin (in western United States) covering a 12-year period (2008-2019) at a high spatial resolution (400 m). The datasets are generated using a downscaling framework that uses data-driven models to learn relationships between climate variables and topography. We observe that downscaled datasets of precipitation and mean temperature exhibit smoother spatial gradients compared to their coarser counterparts. Additionally, we also observe that when downscaled datasets are reaggregated to the original resolution (800 m), the mean residual error is almost zero, ensuring spatial consistency with the original data. Furthermore, the downscaled datasets are observed to be linearly related to elevation, which is consistent with the methodology underlying the original 800 m product. Finally, we validate the spatial patterns exhibited by downscaled datasets via an example use case that models lidar-derived estimates of snowpack. The presented dataset constitutes a valuable resource to resolve fine-sale hydrological gradients in the mountainous terrain of the East-Taylor subbasin, which is an important study area in the context of water security for southwestern United States and Mexico. The dataset is publicly available at https://doi.org/10.15485/1822259 (Mital et al., 2021). [ABSTRACT FROM AUTHOR]

Objectives: We aim to estimate geographic variability in total numbers of infections and infection fatality ratios (IFR; the number of deaths caused by an infection per 1,000 infected people) when the availability and quality of data on disease burden are limited during an epidemic. Methods: We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek testing. We demonstrate the robustness, accuracy, and precision of this framework, and apply it to the United States (U.S.) COVID-19 pandemic to estimate countylevel SARS-CoV-2 IFRs. Results: The estimators for the numbers of infections and IFRs showed high accuracy and precision; for instance, when applied to simulated validation data sets, across counties, Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928, respectively, and they showed strong robustness to model misspecification. Applying the county-level estimators to the real, unsimulated COVID-19 data spanning April 1, 2020 to September 30, 2020 from across the U.S., we found that IFRs varied from 0 to 44.69, with a standard deviation of 3.55 and a median of 2.14. Conclusions: The proposed estimation framework can be used to identify geographic variation in IFRs across settings. [ABSTRACT FROM AUTHOR]